Objective: To investigate whether monocyte CD11c (mCD11c) can serve as a promising biomarker for the diagnosis and prognosis of sepsis, distinguishing it from non-infectious inflammatory conditions. Methods: A prospective, observational cohort study was conducted using a discovery cohort (sepsis, mild infection, patients after cardiovascular surgery, recovered sepsis patients, and healthy controls) and a validation cohort (sepsis, mild infection, and patients after cardiovascular surgery). Peripheral blood samples were analyzed using Cytometry by Time-of-Flight (CyTOF), single-cell RNA sequencing, and flow cytometry to assess the immune cell composition and mCD11c expression. Clinical data and outcomes were collected for analysis. Results: The discovery cohort showed a significant downregulation of mCD11c in patients with sepsis. The validation cohort confirmed a lower mCD11c% in sepsis than in the other groups. Receiver operating characteristic (ROC) curve analysis showed that mCD11c had a higher AUC (0.939, P < 0.001) than traditional markers in distinguishing sepsis from non-infectious inflammation. mCD11c% was an independent prognostic factor for 7-day mortality (P < 0.05), with significant differences in survival rates between patients with mCD11c% above and below 96.445%. Conclusion: mCD11c is a promising biomarker for early sepsis diagnosis and short-term survival prediction, outperforming the traditional markers. Larger multicenter studies are needed to validate these findings and to explore their potential as intervention targets.

Sepsis is characterized by a systemic host response to infection. Monocytes, as major mediators of acute infection, are implicated in complications among critically ill patients. Identifying key monocyte subsets and their activation states is essential for diagnosis and delineating new therapeutic targets for sepsis. Here, single cell transcriptome sequencing and mass cytometry are used to assess alterations in the composition and function of peripheral monocytes of patients with sepsis, and CD38high monocytes in circulation are specifically accumulated within the first 24 h of sepsis. CD38high monocytes are detectable by conventional flow cytometry to discriminate sepsis and sterile inflammation, and are associated with 28-day mortality in bacterial sepsis. Targeting CD38 therapy markedly reduces inflammatory response in primary monocytes and in sepsis mice model. Mechanistically, CD38high monocytes in sepsis exhibit hyperactivated glycolysis with activation of hypoxia-inducible factor-1α (HIF-1α) due to NAD+ consumption. Glycolytic metabolite methylglyoxal (MGO) is found to regulate expression of CD38, establishing a CD38-HIF-1α/glycolysis/MGO loop that exacerbates sepsis-induced immune dysregulation. These findings demonstrate that CD38high monocytes might serve as a candidate diagnostic biomarker and therapeutic target for sepsis.

Sepsis is a critical condition associated with high morbidity and mortality, emphasizing the need for reliable biomarkers for its diagnosis and prognosis. This study uses advanced immunological techniques to evaluate monocytic CD39 (mCD39) expression as a potential marker in sepsis. This prospective observational cohort study included 206 participants from the First Affiliated Hospital, Zhejiang University School of Medicine between April 2022 and September 2023. Participants were categorized into four groups: healthy donors, patients with mild infections, post-cardiac surgery patients (non-infectious inflammation), and sepsis patients. Peripheral Blood Mononuclear Cells were analyzed using mass cytometry time-of-flight (CyTOF) with a 42-marker immune panel and flow cytometry targeting monocytes. Statistical analyses included ROC curves for diagnostic and prognostic performance and Kaplan–Meier survival analysis for prognostic evaluation. Sepsis patients exhibited significantly lower monocytic CD39 expression than mild infection and post-surgery groups (p < 0.05). The diagnostic performance analysis revealed that mCD39 effectively distinguished sepsis from mild infection (AUC = 0.877) and non-infectious inflammation (AUC = 0.935). Prognostic analysis identified low mCD39 expression as a strong predictor of short-term survival, with a 7-day survival AUC of 0.85 (p = 0.037). Kaplan–Meier analysis showed that sepsis patients with low mCD39 expression had significantly lower 28-day survival rates (56.7

Purpose:Pneumonia is common in ICU patients with neurological dysfunction, but differences in pulmonary pathogen distribution in this population remain unclear. This study aimed to compare pathogen profiles, clinical features, and outcomes between ICU patients with and without neurological dysfunction. Methods:This regional multicenter retrospective study included adult patients with severe pneumonia admitted to intensive care units (ICUs) in 11 hospitals across Zhejiang and Henan Provinces in mainland China between December 2018 and November 2023. All patients required invasive mechanical ventilation and underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS). Patients were classified into neurological dysfunction (ND) and without neurological dysfunction (WND) groups. Clinical characteristics, microbiological findings, and outcomes were compared. Propensity score matching (PSM) and Cox regression were used to assess prognosis. Results:Among 1737 patients, 636 (41.8%) were in the ND group. After PSM, the ND group showed a higher 28-day ICU mortality rate and shorter time to death compared to the WND group. However, ND was not identified as an independent risk factor for 28-day mortality in Cox analysis. The prevalence of Acinetobacter baumannii, Klebsiella pneumoniae, Burkholderia, Serratia marcescens, Elizabethkingia, Clostridium spp. and Ureaplasma was higher in ND patients. Significant differences in the prevalence of Haemophilus influenzae, Fusarium oxysporum, Fusobacterium nucleatum, Porphyromonas gingivalis, Mycobacterium abscessus, Escherichia coli, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were also observed. Conclusion:ICU patients with neurological dysfunction exhibited distinct pulmonary pathogen profiles and worse outcomes. These findings may inform empirical antimicrobial strategies. Further prospective studies are warranted to validate these results.

Purpose: The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. Methods: This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. Results: Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69- 133.78) and 33.82 (0.83-126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were > 2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low. Conclusions: Inhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

The purpose of this project was to characterize the longitudinal dynamic serum sodium trajectory of sepsis patients with lactic acidosis (LA) admitted to the intensive care unit (ICU), and to explore the association between these trajectories and the 30-day mortality rate of patients. Data on patients admitted to the ICU with a diagnosis of LA combined with sepsis from 2008-2019 were collected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Patients admitted to the ICU for > 24 hours and for the first time were sorted into 3 groups based on their serum sodium levels at admission. The Group-based Trajectory Modeling (GBTM) method was applied to analyze the trajectory changes of serum sodium in each group of patients over 72 hours. Patients' survival differences between different trajectory groups were compared using Kaplan-Meier (K-M) survival curves. Subgroup analysis was carried out to determine the influencing factors of the relationship between dynamic changes in serum sodium and patient survival. This study included 514 patients with LA complicated by sepsis, who were clustered into three groups based on their admission serum sodium levels, with 378 patients in the normal blood sodium (135-145 mEq/L) group, 116 patients in the hyponatremia (< 135 mEq/L) group, and 20 patients in the hypernatremia (> 145 mEq/L) group. GBTM analysis generated three different serum sodium trajectories. The K-M curve results demonstrated that patients with relatively stable serum sodium levels within the normal range (Class 2) had lower 30-day mortality compared to groups with larger fluctuations in sodium levels (Class 1, Class 3). Subgroup analysis uncovered notable interactions (P < 0.05) between different trajectories of serum sodium and covariates such as race, marital status, Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA), renal replacement therapy (RRT), congestive heart failure, kidney disease, liver disease, and diabetes. Among patients with LA complicated by sepsis, those with stable and normal fluctuations in serum sodium levels had better 30-day survival rates. GBTM is a refined method to describe the evolution of serum sodium and its association with clinical outcomes, which may enhance the current understanding of blood sodium level regulation.

Introduction Post-neurosurgical central nervous system (CNS) infection caused by multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacteria remains a major clinical challenge. This study describes our experience of treating such patients with combined intraventricular (IVT) and intravenous (IV) polymyxin B administration. Methods This retrospective study included six patients with post-neurosurgical CNS infections of carbapenem-resistant Acinetobacter baumannii (CRAB) or carbapenem-resistant Klebsiella pneumoniae (CRKP). All patients were treated in the intensive care unit (ICU) of First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) between November 2020 and November 2021, and all received IVT plus IV polymyxin B. Data including patients' characteristics, therapeutic process, symptoms, cerebrospinal fluid (CSF) examination, laboratory tests, and complications were collected. Results Six patients with post-neurosurgical CNS infection were enrolled in the study. The patients comprised five males and one female, and the average age was 58 years (range, 38–73 years). Four out of the six cases were CRAB-positive in CSF culture, while two cases were CRKP-positive. The mean duration of polymyxin B administration was 14 ± 5.69 days (range, 6–20 days). The average period of patients reaching CSF sterilization was 10.33 ± 3.67 days (range, 5–14 days). All six cases were cured without acute kidney injury or epilepsy. Conclusion IVT plus IV polymyxin B is a safe and effective treatment for post-neurosurgical patients with intracranial infection caused by MDR/XDR Gram-negative bacteria.

Background: Hemodynamic management is of paramount importance in patients with septic shock. Echocardiography has been increasingly used in assessing volume status and cardiac function. However, whether the utilization of echocardiography has an impact on prognosis is unknown. Thus, we intended to explore its effect on the outcomes of patients with septic shock. Methods: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. Septic shock patients were divided into two groups according to the usage of echocardiography during the onset of septic shock. The primary outcome was 28-day mortality. Secondary outcomes included the usage of inotropes, ventilation-free and norepinephrine-free time, and fluids input. Propensity-score matching was used to reduce the imbalance. Results: Among 3,291 eligible patients, 1,289 patients who underwent echocardiography (Echo), and 1,289 who did not receive the Echo, had similar propensity scores and were included in the analyses. After matching, the Echo group had a significantly lower 28-day mortality (33.2% vs. 37.7%, P=0.019). More patients in the Echo group received pulmonary artery catheter (PAC) (4.2% vs. 0.2%, P<0.001) and inotropes (17.8% vs. 7.1%, P<0.001). In the survival analysis, Echo utilization was associated with improved 28-day mortality [hazard ratio (HR): 0.83; 95% confidence interval (CI), 0.73-0.95, P=0.005]. A reduced likelihood of 28-day mortality in patients with Echo vs. those without Echo was maintained either when excluding patients receiving multiple echocardiography scans (HR, 0.82; 95% CI, 0.72-0.94; P=0.004) or when excluding patients undergoing PAC or pulse index continuous cardiac output (PiCCO) (HR, 0.87; 95% CI, 0.76-0.99; P=0.034). Conclusions: Utilization of echocardiography was associated with improved 28-day outcomes in patients with septic shock.

Objective This study aimed to examine the mechanism of diaphragmatic dysfunction in sepsis due to severe acute pancreatitis (SAP) with intra-abdominal hypertension (IAH) in a rat model. Methods The rats were assigned at random to four groups: (1) control (n=5), (2) SAP (n=5), (3) SAP+IAH (n=5), and (4) SAP+IAH+SS-31 (n=5). Length and force output of the diaphragm were analysed in vivo. Histopathological examinations were performed by haematoxylin-eosin. Oxidative stress levels related to protease in diaphragmatic mitochondria were detected with a colorimetric technique. Results In the septic rat model due to SAP complicated by IAH, myofibres were increased. Muscle contractile function was significantly lower in the SAP+IAH group compared with the SAP and control groups. Glutathione peroxidase and superoxide dismutase levels were significantly lower and malondialdehyde levels were higher in the SAP and SAP+IAH groups compared with the control group. Notably, SS-31 could reverse atrophy of myofibres in SAP+IAH rats, as well as contractile dysfunction and mitochondrial dysfunction in the diaphragm. Conclusions Diaphragmatic structure and biomechanics are altered in septic rats due to SAP and IAH. This finding is mainly due to an increase in release of mitochondrial reactive oxygen species.

湖州 小逸妈妈 我的女儿小逸在上课时突然晕倒了.送到医院检查,医生说女儿患了线粒体肌病.请问这是一种什么病? 浙江大学医学院邵逸夫医院 林玲 郦航洋 高芳芳 线粒体疾病往往是由于线粒体DNA突变,影响了线粒体的功能.如果病变以侵犯骨骼肌为主,称为线粒体肌病.如病变同时累及中枢神经系统,则称为线粒体脑肌病. 线粒体肌病的症状包括: 肌无力.这是这种病最明显的症状,一般先四肢无力,然后发展至全身肌肉无力.往往在轻微活动后就感到疲乏,休息后缓解.可能还有肌肉酸胀痛、压痛,少数病人会出现肌肉萎缩.

BACKGROUND:Blood pressure control is an essential therapy for patients with acute type B aortic dissection (ABAD) and should be maintained throughout the entire treatment. Thus, vast majority current guidelines recommend control the blood pressure to lower than 140/90 mmHg. Theoretically, a much lower target may further decrease the risk of propagation of dissection. However, some argued that too lower blood pressure would compromise the organ perfusion. Thus, there is no unanimous optimal target for blood pressure in patients with ABAD so far. The present study aimed to investigate the optimal blood pressure target for patients with ABAD, in the hope that the result would optimize the treatment of aortic dissection (AD).METHODS:The study is a multi-center randomized controlled clinical trial. Study population will include patients with new diagnosed ABAD and hypertension. Blocked randomization was performed where intensive blood pressure control (<120 mmHg) with conventional blood pressure control (<140 mmHg) were allocated at random in a ratio of 1:1 in blocks of sizes 4, 6, 8, and 10 to 360 subjects. Interim analysis will be performed. The primary outcome is a composite in-hospital adverse outcome, including death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge. While the secondary outcomes include the aortic size, lower extremity or visceral ischemia, retrograde propagation into aortic arch or ascending aorta, mortality in 6 months and 1 year, intensive care unit (ICU) length of stay, total length of hospital stay, creatinine level, and surgical or endovascular intervention.ETHICS AND DISSEMINATION:The study was approved by the institutional review board of Sir Run Run Shaw Hospital (approval number: 20160920-9). Informed consent will be obtained from participants or their next-of-kin. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.TRIAL REGISTRATION:NCT03001739 (https://register.clinicaltrials.gov/).

Background: Acute aortic disease is a common but challenging entity in clinical practice. Titration the blood pressure and heart rate to a target level is of paramount importance in the acute phase regardless of whether the patient will undergo a surgery or not eventually. In addition to the initially intravenous beta-blockers, parenteral infusion of nicardipine and urapidil are the most common used antihypertensive therapy currently in mainland China. However, few empirical data was available with respect to the different effect on patients' outcome of the two antihypertensive strategies. Specifically given the deleterious reflex tachycardia of vasodilators which may increase force of ventricular contraction and potentially worsen aortic disease. Therefore, this study was aimed to evaluate the difference of the abovementioned two antihypertensive strategies on the outcome of patients with aortic disease.Methods: All patients with new diagnosed aortic diseases presented to our hospitals from January 1, 2013 to June 30, 2014 were retrospectively reviewed. The antihypertensive strategies and their association with patients' outcomes were evaluated with logistics regression.Results: A total of 120 patients with new diagnosed aortic disease were included in the study. Of them, 47 patients received urapidil while 73 patients received nicardipine antihypertensive therapy. Patients with nicardipine were more quickly to reach the target blood pressure level than those treated with urapidil ( median, 18 vs. 35 min, P=0.024). After adjustment for patient demographics, co-morbidity, involved extend of aorta, interventional strategies, antihypertensive therapy with nicardipine ( with urapidil as reference) for patients with aortic disease was significantly associated with high esmolol cost [odds ratio (OR): 6.2, 95% confidence interval (CI), 1.8-21.6, P=0.004] and longer ICU length of stay (LOS) (OR: 3.9, 95% CI, 1.5-10.3, P=0.006). However, there was no significant correlation between nicardipine use and ICU mortality (OR: 0.3; 95% CI, 0.1-1.4, P=0.123).Conclusions: Although nicardipine achieved the target blood pressure level more quickly than urapidil for patients with aortic disease, it was associated with more esmolol use and longer ICU LOS.